JunB condensation attenuates vascular endothelial damage under hyperglycemic condition.

Endothelial damage is the initial and crucial factor in the occurrence and development of vascular complications in diabetic patients, contributing to morbidity and mortality. Although hyperglycemia has been identified as a damaging effector, the detailed mechanisms remain elusive. In this study, identified by ATAC-seq and RNA-seq, JunB reverses the inhibition of proliferation and the promotion of apoptosis in human umbilical vein endothelial cells treated with high glucose, mainly through the cell cycle and p53 signaling pathways. Furthermore, JunB undergoes phase separation in the nucleus and in vitro, mediated by its intrinsic disordered region and DNA-binding domain. Nuclear localization and condensation behaviors are required for JunB-mediated proliferation and apoptosis. Thus, our study uncovers the roles of JunB and its coacervation in repairing vascular endothelial damage caused by high glucose, elucidating the involvement of phase separation in diabetes and diabetic endothelial dysfunction.

Similar Aquaporin9 and MAPK Expression Profiles in the Liver of Types 1 and 2 Diabetes Mellitus.

Aquaporin-9 (AQP9) is an aquaglyceroporin that biophysically conducts water, glycerol, and other small solutes. AQP9 is expressed in hepatocytes on the sinusoidal surfaces of hepatocyte plates in the liver, where it is considered responsible for the glycerol uptake in gluconeogenesis. However, limited information is available on the expression and regulating mechanism of AQP9 in different hyperglycemia models. Thus, this study examined the expression patterns of AQP9 and mitogen-activated protein kinase (MAPK) in Types 1 and 2 diabetes mellitus (DM) to clarify the roles and regulating mechanism of AQP9 in gluconeogenesis. Compared with the control group, the AQP9 expression significantly increased in both Types 1 and 2 DM, and the increased expression was associated with the activation of phosphorylated JNK (p-JNK) and the inhibition of phosphorylated p38 (p-p38). By contrast, phosphorylated ERK remained stable in the liver with Type 1 or 2 DM. These effects could be reversed by insulin treatment. That is, insulin downregulated AQP9 by inhibiting p-JNK and activating p-p38. The upregulation of AQP9 could be involved in gluconeogenesis and co-regulated by the JNK and p38 MAPK pathway in both Types 1 and 2 DM.

Phosphorylation of p38 MAPK mediates aquaporin 9 expression in rat brains during permanent focal cerebral ischaemia.

Aquaporin 9 (AQP9), an aquaglyceroporin, is an important aquaporin in the brain. This study examined the expression patterns of AQP9 and p38 mitogen-activated protein kinases (MAPK) in ischaemic brains from rats with permanent middle cerebral artery occlusion (pMCAO) to elucidate the function and regulation of AQP9 after ischaemia. AQP9 was co-localised with glial fibrillary acidic protein-positive astrocytes and neuronal nuclei-positive neurons in rat brains. Expression of AQP9 increased continuously until 24 h after pMCAO in the ischaemic core region and the border region. Importantly, this increase in expression of AQP9 correlated with brain oedema. AQP9 expression was predominant in astrocytes within 3 h after pMCAO and then in neurons 6 h after pMCAO. Phosphorylated p38 MAPK was also induced in the ischaemic core region and the border region at different time points after pMCAO. Interestingly, intracerebroventricular injection of the p38 MAPK inhibitor SB203580 attenuated AQP9 expression after pMCAO. Taken together, these results indicate that dynamic changes in AQP9 expression, mediated in part via the p38 MAPK signal transduction pathway, may contribute to the development of cerebral oedema after brain ischaemia.